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Evaluation of the role of TLR4 and TLR 7/8 receptors in individuals infected with SARS-CoV-2

Grant number: 20/15199-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2021
Effective date (End): December 31, 2021
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Nátalli Zanete Pereira
Grantee:Julia Cataldo Lima
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The SARS-Cov-2 pandemic represents a major epidemiological challenge worldwide and the disease caused by this virus, COVID-19, has already killed more than 1 million people. Innate immunity represents a powerful line of defense against viral infections and can be determinant in several pathologies. Despite being a respiratory virus, the systemic character of COVID-19 stands out. TLR4, an innate immunity receptor, is fundamental in responses against bacteria, recognizes LPS and produces inflammatory factors. Experimental model data reveal the influence of ACE2 enzyme on LPS / TLR4 axis. In SARS-Cov-2 infection, the virus recruits ACE2 and uses this enzyme as an input receptor. Our hypothesis is that the LPS / TLR4 pathway may be affected by the difference in ACE2 levels. Thus, we will evaluate the role of LPS (TLR4 ligand) in inflammatory cytokines production. In addition, we also aim to analyze the expression of antiviral factors. Viral recognition, performed by TLR7/8, triggers IFN production, which in turn, induces antiviral factors production. It has already been described that SARS-Cov-2, as a form of immune escape, can limit IFN production. It is our goal to evaluate the constitutive expression and induce these ISGs expression, by stimulating CL097 (TLR7/8 agonist) or type I IFN. Understanding the innate immune response, with an emphasis on antiviral factors and modulation by TLR ligands, it can promote possible protection correlates and provide subsidies to develop new therapies. (AU)